A variety of human and animal rotaviruses have been grown in cell culture and are available for further study as potential vaccine candidates. In a previous study in adult volunteers immunologic correlates of resistance were defined. In the current studies these correlates (serum antibodies measured by a variety of techniques the most important being neutralization in tissue culture) were used to select volunteers for evaluation of candidate vaccine strains. Our intent was to identify rotaviruses that were capable of infecting susceptible adults and inducing immunity without the development of disease. Three candidate viruses were evaluated, the human Wa rotavirus (serotype 1) and two animal rotaviruses, the bovine UK rotaviruses and the rhesus rotavirus. The human Wa rotavirus and the rhesus rotavirus infected susceptible adult volunteers and induced a rotavirus antibody response but these viruses did not cause disease. The bovine UK rotavirus did not appear to infect adult volunteers. The rhesus rotavirus appears to be promising because it is similar by neutralization to the human serotype 3 rotavirus. Furthermore, the rheusus virus stimulated heterotypic serum rotavirus antibody responses in adult volunteers. Finally, rhesus rotavirus may prove useful as a donor of attenuating genes to reassortant viruses that bear the major neutralization protein (VP7) or a human rotavirus belonging to serotype 1, 2, or 4. In this manner homotypic protection could be provided for each of the human serotypes. Indeed, single gene substitution reassortants are now available for each of the human serotypes. These viruses possess 10 rhesus rotavirus genes and a single human rotavirus gene, the one that codes for neutralization specificity. It is likely that such single gene substitution reassortants will induce immunity to viruses belonging to the serotype of their human rotavirus parent while at the same time they should retain the attenuation of their rhesus rotavirus parent.